We wrote in this blog a few weeks ago about Dr Nicholas Turner’s call for researchers to meet the challenge of triple-negative breast cancer -- the most hard-to-treat type with the worst outlook for women. Dr Turner has expanded on that theme -- along with Dr Jorge Reis-Filho, a former colleague here at The Institute of Cancer Research, London -- in a new review. It makes fascinating reading.
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Breast cancers are usually grouped on the basis of whether the cancer cells express one of three receptors -- human epidermal growth factor receptor 2 (HER2), oestrogen receptor (ER) or progesterone receptor. Breast cancer cells that have none of these hormone receptors are classified as triple-negative.
Only focused on relatively recently, it turns out that triple-negative breast cancers account for around 15% of breast cancer cases. Studies also show that triple-negative cancers are more likely to spread beyond the breast and to recur after treatment than other forms. Following surgery to remove the cancer, chemotherapy is currently the best treatment option and is usually given in combination. But although adjuvant chemotherapy reduces the relative risk of death by approximately 30%, there still isn’t a particular chemotherapy combination that doctors recommend.
Dr Turner says improvements in hormone positive breast cancer treatments have come on over the last five years owing to the progress made with targeted therapies. But improvements in survival for patients with triple-negative breast cancer have plateaued because of the absence of promising systemic therapies, and disappointingly, there are no current treatments in late-stage clinical trials for this type of breast cancer.
So how can we kick start the progress that has halted over the last couple of years? Dr Turner is suggesting that we combine traditional research approaches, such as pathological classification, with more focus on a deeper understanding of the genetic profiles of individual cancers. As I learned more about the molecular diversity of triple-negative breast cancer, I realised that researchers have a real challenge on their hands when it comes to classifying this form of the disease. Not only does it have at least six gene expression subtypes, there are also multiple genetic drivers to consider, such as mutations, deletions or amplifications in genes including TP53, PTEN and MYC. This becomes even more complex when researchers are revealing that there are associations between gene expression subtypes and genetic drivers – all of which could be targeted by different treatments. Only now are we beginning to realise the high heterogeneity in triple-negative tumours and the major challenge this poses to the development of targeted therapies.
Undaunted, Dr Turner is extremely excited and optimistic about finding new treatments. He believes that we need to bring molecular stratification into the clinic potentially with both genetic and gene expression subtypes. Armed with this knowledge, we will be able to design smarter clinical trials of targeted treatments, picking out the most appropriate therapy for each individual patient.